CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Patent Application 61/586,851, filed January 16, 2012, which is incorporated herein by reference

FIELD OF THE INVENTION

The present invention relates generally to acoustic beams and particularly to generation and control of focused acoustic beams.

BACKGROUND

Focused ultrasound (FUS) technology is based on heating a small volume of tissue (typically inside a living body) using ultrasonic energy. If correctly targeted, FUS heats a small volume up to coagulation level (at about 57°C) without causing tissue damage outside the treated volume. FUS systems are currently used clinically for treatment of uterine fibroids, and may be used, as well, for ablation of tumors in the breast, brain, liver and prostate and for the palliation of pain in bone metastasis.

FUS generally uses a phased array of acoustic transducers to generate a beam with the desired focal properties. Various methods are known in the art for driving and controlling the transducers for this purpose. For example, PCT International Publication WO 2011/138784, whose disclosure is incorporated herein by reference, describes such a method of operating a multi-focused acoustic wave source. A plurality of target acoustic pressures are provided, to be applied on a plurality of regions of interest in at least one cellular tissue. A transmission pattern of multi-focal acoustic energy is computed according to these target acoustic pressures.

SUMMARY

Embodiments of the present invention provide methods, apparatus and software that enable enhanced control and performance in generation of shaped acoustic beams.

There is therefore provided, in accordance with an embodiment of the present invention, a method for irradiation, which includes defining a target to be irradiated by acoustic energy from an acoustic emitter. An obstacle zone is identified in a path of acoustic waves between the acoustic emitter and the target. An excitation waveform to be applied to the acoustic emitter is computed so as to cause the acoustic energy emitted by the acoustic emitter to focus on the target while bypassing the obstacle zone. In some embodiments, computing the excitation waveform includes generating a three- dimensional (3D) continuous acoustic hologram to be formed by the emitted acoustic waves. In a disclosed embodiment, generating the 3D continuous acoustic hologram includes modeling a pressure exerted by the acoustic waves both at the target and in the obstacle zone so as to maximize the pressure at the target while minimizing the pressure in the obstacle zone. Additionally or alternatively, generating the 3D continuous acoustic hologram includes applying an iterative algorithm to simulate a propagation of the acoustic waves between the acoustic emitter and a target. Applying the iterative algorithm may include computing a 3D angular spectrum model of a pressure field associated with the acoustic waves.

The method may include applying the excitation waveform to the acoustic emitter so as to focus ultrasonic energy at a location in a body of a living subject, wherein the ultrasonic energy is focused so as to ablate tissue at the location. Typically, the acoustic emitter includes a phased array of acoustic transducers.

There is also provided, in accordance with an embodiment of the present invention, a method for irradiation, which includes defining an irradiation pattern to be formed by acoustic energy emitted from an acoustic emitter. An excitation waveform to be applied to the acoustic emitter is computed by generating a three-dimensional (3D) continuous acoustic hologram corresponding to the defined irradiation pattern.

Generating the 3D continuous acoustic hologram typically includes applying an iterative algorithm to simulate a propagation of the acoustic waves between the acoustic emitter and a target. The irradiation pattern may have a predefined non-cylindrical shape or multiple focal points.

There is additionally provided, in accordance with an embodiment of the present invention, apparatus for irradiation, including an acoustic emitter and a driver, which is configured to drive the acoustic emitter to emit acoustic energy in accordance with an excitation waveform. A processor is configured to accept a definition of a target to be irradiated by the acoustic energy and an identification of an obstacle zone in a path of acoustic waves between the acoustic emitter and the target, and to compute the excitation waveform to be applied to the driver so as to cause the acoustic energy emitted by the acoustic emitter to focus on the target while bypassing the obstacle zone.

There is further provided, in accordance with an embodiment of the present invention, a computer software product, including a non-transitory computer-readable medium in which program instructions are stored, which instructions, when read by a computer, cause the computer to accept a definition of a target to be irradiated by acoustic energy from an acoustic emitter and an identification of an obstacle zone in a path of acoustic waves between the acoustic emitter and the target, and to compute an excitation waveform to be applied to the acoustic emitter so as to cause the acoustic energy emitted by the acoustic emitter to focus on the target while bypassing the obstacle zone.

The present invention will be more fully understood from the following detailed description of the embodiments thereof, taken together with the drawings in which:

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is schematic pictorial illustration of a system for FUS therapy, in accordance with an embodiment of the present invention;

Fig. 2 is a schematic side view of a transducer array generating a focused acoustic beam that bypasses an obstacle zone, in accordance with an embodiment of the present invention;

Fig. 3 is a flow chart that schematically illustrates a method for generating a focused acoustic beam, in accordance with an embodiment of the present invention;

Fig. 4 is a flow chart that schematically illustrates a method for computing an excitation waveform to be applied to an acoustic transducer array, in accordance with an embodiment of the present invention; and

Fig. 5 is a schematic representation of phases and amplitudes of acoustic waveforms that are generated at three different planes in a focused ultrasound system, in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS

It is generally desirable in FUS to minimize collateral heating outside the focal region. Several FUS applications, such as treatments of the brain and the liver, suffer from the existence of ultrasound absorbers in the acoustic path between the transducer and the focus. These absorbers are a potential risk in FUS therapy since they can cause unwanted heating outside the focal region.

Embodiments of the present invention that are described herein provide an acoustic- simulation-based solution for reducing heating of absorbers in the path of focused acoustic waves. These embodiments use 3D continuous acoustic holograms, which may then be produced using a planar phased-array of acoustic transducers. The holograms may be generated using a computer algorithm based on the Gerchberg-Saxton (GS) algorithm, and particularly the weighted Gerchberg-Saxton (GSW) algorithm. In the disclosed embodiments, algorithms for computer-generated holography (CGH) are adapted to fit linear acoustical equations in order to generate arbitrary acoustical intensity patterns in space. The algorithms use an angular spectrum method to simulate the acoustical field backward to and forward from a phased array of acoustic transducers. The holographic solution for the acoustic field is implemented by applying a suitable (electrical) excitation waveform to the phased array of ultrasound transducers, as described above, or alternatively by a passive material with multiple thicknesses or by an ultrasound transducer designed for generation of a specific hologram.

The acoustic-hologram approach provided by embodiments of the present invention may be used to reduce acoustic energy density on obstacles inside a focused ultrasound path. In therapeutic ultrasound applications, for example, such obstacles could include calcifications, rib bones and/or air-bubbles that have different acoustic properties from the surroundings. Heat could be generated at the obstacle during the FUS therapy and cause unwanted damage outside the focal region. In the disclosed embodiments, energy density on the obstacle is reduced, and an acoustic intensity pattern may be generated with a desired FUS intensity pattern at the focal plane and near-zero intensity at the obstacle region.

Several other ultrasound applications can use the techniques described herein in order to improve their performance by generating better acoustic fields:

• Improve FUS therapy efficiency using shaped focal intensities, such as a spherical focal region instead of the standard cylindrical focus, could yield more effective ablation for a given energy input (taking heat perfusion and diffusion into account).

• Generation of ultrasound intensity patterns for neural stimulation.

• Generation of multiple focal points for creating an array of multiple wells, such as for targeted drug delivery.

Fig. 1 is schematic pictorial illustration of a system 20 for FUS therapy, in accordance with an embodiment of the present invention. An acoustic emitter 24 is applied to treat a target site, which in the pictured embodiment is located in the abdomen of a patient 22. Alternatively, emitter 24 may be applied to other locations in the body (and the principles of the present invention may similarly be used in other, non-medical applications of FUS). Emitter 24 in this embodiment is assumed to comprise a phased array of miniature transducers 26, as shown in the inset. Although a regular, rectilinear array is shown in the figure, transducers 26 may alternatively be arranged in other sorts of array configurations, as are known in the art. A driver 28 provides electrical signals to drive each transducer 26 with the appropriate amplitude and phase to generate ultrasonic waves that will focus on the target site. These amplitudes and phases are defined by waveforms computed by a processor 30, using methods of three-dimensional (3D) continuous acoustic hologram generation that are described further hereinbelow. Driver 28 comprises suitable frequency generation and amplification circuits, as are known in the art of acoustic phased arrays. Typically, processor 30 is embodied in a general-purpose computer, having a memory and suitable input and output interfaces, and the amplitudes and phases of the drive signals are computed by the processor under the control of appropriate software. This software may be downloaded to the computer in electronic form, over a network, for example. Alternatively or additionally, the software may be stored on tangible, typically non-transitory, computer-readable media, such as optical, magnetic, or electronic memory media. Further alternatively or additionally, at least some of the functions of processor 30 may be implemented in dedicated or programmable hardware logic circuits.

Fig. 2 is a schematic side view of emitter 24 generating a focused acoustic beam 32 that is focused onto a target 34 while bypassing an obstacle zone 36, in accordance with an embodiment of the present invention. The target may be, for example, a tumor that is to be ablated by FUS, while the obstacle zone is an ultrasound-absorbing area of hard or soft tissue between the body surface and the target. The locations of target 34 and obstacle zone 36 may be ascertained, for example, by magnetic resonance imaging (MRI) or other techniques that are known in the art, and may be input to processor 30 by an operator of system 20 based on such images.

This figure illustrates a number of terms of reference that are used in the present description and in the claims. In computing the drive signals to be applied to transducers 26, processor constructs a 3D acoustic hologram with reference to three planes: the plane of transducers 26 from which the acoustic energy is emitted; a target plane 35; and an obstacle plane 38. The dashed arrows in the figure schematically represent the flow of acoustic energy between these planes, generated as a superposition of the waves produced by the different transducers 26. The acoustic energy is said to "bypass" obstacle zone 36 in the sense that the energy in plane 38 is distributed so as to minimize the energy density within the obstacle zone, while the energy density in other areas of the plane surrounding the obstacle zone is substantially higher. Typically, the energy density in obstacle zone 36 is at least 50% less than in the surrounding area of obstacle plane 38, and in some conditions the energy density in the obstacle zone may be 80% less or even 90% less than in the surrounding area. In this manner, deposition of acoustic energy on target 34 may be maximized while minimizing the loss of energy due to absorption in obstacle zone 36.

Fig. 3 is a flow chart that schematically illustrates a method for generating a focused acoustic beam, in accordance with an embodiment of the present invention. An operator of system 20 defines an irradiation target, such as target 34, at a target definition step 40. The definition typically indicates the location of the target relative to emitter 24, as well as the desired target shape, which may be spherical, cylindrical, or of some other geometrical shape. Optionally, multiple targets of this sort may be irradiated simultaneously or sequentially by appropriate control of emitter 24. The operator also defines an obstacle zone, such as zone 36, between emitter 24 and target 34. As noted earlier, the obstacle and target zones may be defined with the aid of MRI or other imaging modalities. Alternatively or additionally, these zones may be identified automatically by processor 30 by means of image processing or other location methods that are known in the art.

Based on the target and obstacle coordinates, processor 30 computes the electrical excitation waveform that is to be applied to transducers 26, at a waveform computation step 44. The computation, as noted earlier, involves an iterative process of continuous 3D computer- generated holography, which is described in greater detail hereinbelow with reference to Fig. 4. Further aspects of this process, and particularly mathematical formalisms that may be used in implementing the process, are described in the above-mentioned U.S. Provisional Patent Application 61/586,851 and are described below in an Appendix.

The iterative process of step 44 proceeds until a satisfactory solution is found, i.e., until an excitation waveform is derived that, when tested by mathematical simulation, gives a distribution of energy on target 34 and on obstacle zone 36 that meets predefined criteria. For example, these criteria may specify a minimum threshold percentage of the total emitted energy from emitter 24 that should be incident on target 34 and a maximum threshold percentage that may be incident on obstacle zone 36. Alternatively or additionally, the iterative process may be halted after a certain number of iterations and tested for compliance with the threshold criteria. Once a satisfactory solution is found, the excitation waveform thus derived is applied by driver 28 to emitter 24.

Reference is now made to Figs. 4 and 5, which schematically show details of waveform computation step 44, in accordance with an embodiment of the present invention. Fig. 4 is a flow chart, while Fig. 5 presents maps of the phases and amplitudes generated at target plane 35, obstacle plane 38, and a transducer plane 70, defined by the array of transducers 26. As noted earlier, further details of this computational approach are presented in the above- mentioned provisional patent application and in the Appendix below.

The computation of the excitation waveform uses an iterative approach based on the weighted Gerchberg-Saxton (GSW) algorithm. In this approach, acoustic pressure maps are propagated back and forth between target plane 35, obstacle plane 38, and the transducer plane 70. These maps express the complex pressure field p(r) in any given plane in 3D space (wherein r is the 3D Cartesian coordinate) using an inverse Fourier transform of the angular spectrum by the expression:

p(r) = ^k k _x k _v (1)

wherein p{k _x , ky , zj is the 2D Fourier transform of p(r) over x,y in plane z. This expression gives a continuous representation of the pressure in each 2D plane, which is extended to form a 3D continuous acoustic hologram by incremental backward and forward projection along the z- axis, as given by:

To begin the process of computing the excitation waveform, the geometries of target 34 and obstacle zone 36 are defined, at a problem definition step 50. Processor 30 then adjusts the pressure map in obstacle plane 38 to satisfy the desired condition that the acoustic pressure in obstacle zone 36 be zero, at a pressure setting step 52. The phase in plane 38 may have any arbitrary value. Processor 30 modifies the amplitude of the pressure map in target plane 35 to give optimal focus of the acoustic pressure on target 34, at a focus optimization step 54. The pressure amplitudes in obstacle plane 38 and target plane 35, with zero amplitude in the obstacle zone and maximal amplitude on the target, are represented respectively by maps 72 and 74 in Fig. 5. Initially, steps 52 and 54 may be carried out arbitrarily, but in subsequent iterations through these steps, the modifications of the pressure map in planes 38 and 35 are performed while maintaining continuity with the forward-propagated pressure from the plane of transducers 26. Details of the mathematical process by which the amplitudes at planes 35 and 38 are computed and modified are presented in the above-mentioned provisional patent application and in the Appendix below.

Processor 30 projects the pressure maps from planes 35 and 38 back to the plane of transducers 26, at a back-projection step 56. The projection uses equation (2), while weighting the pressure maps from planes 35 and 38 to give a combined pressure result at the transducer plane:

(3) wherein B _m is the weight coefficient of plane m , and d _m is the distance of the plane from transducers 26. In the present case, M — 2 , corresponding to plane 35 and plane 38. The inventors have found that setting the weight of the obstacle plane to be three times the weight of the target plane gives good results, but other weights may alternatively be used. The application of weights in equation (3) is characteristic of the GSW algorithm that is used in the method of Fig. 4. The resulting amplitude and phase of the waveform in transducer plane 70 are illustrated by maps 76 and 78, respectively, in Fig. 5.

After generating the continuous transducer-plane pressure map in this manner, processor 30 modifies the map to match the physical properties of the transducers, at a transducer plane modification step 58. This step accounts for the fact that the transducers are of finite size (i.e., finite aperture), and that the amplitude and phase of the drive signals generated by driver 28 may be limited and quantized. For example, in some experiments conducted by the inventors, transducers 26 had only binary amplitudes: either on or off. In this case, a threshold function is applied to the pressure map computed at step 56, and transducers with amplitudes below the threshold are simply zeroed (closed). The amplitude of the transmitting element may be set to one or zero according to the following equation:

where Afc is the average amplitude calculated on the surface of element k , A is the average transducer amplitude, and C is a user-defined closing elements coefficient ( C > 0 ). The modified amplitude and phase waveforms resulting from this step are illustrated by maps 82 and 84 in Fig. 5.

Processor 30 now projects the modified pressure map at transducer plane 70 forward to obstacle plane 38 and target plane 35, at a forward projection step 60, again using equation (2). The forward-projected pressure waveforms following this step are represented by amplitude and phase maps 86 and 88 at the obstacle plane and 90 and 92 at the target plane. The processor checks the resulting fields at planes 38 and 35 to determine whether they satisfy the predefined completion criteria, as explained above, at a completion step 62. If not, the processor returns to steps 52 and 54, to modify the pressure maps at planes 35 and 38, followed by back-projection as explained above. Typically, at these steps, the amplitudes are adjusted in the manner described above, as illustrated by amplitude maps 72 and 74, while the phases computed at step 60 are maintained, as illustrated by phase maps 94 and 96.

Once the completion criteria are met, processor 30 proceeds to step 46 (Fig. 3), wherein the excitation waveform corresponding to the pressure map computed at the latest iteration through step 58 is applied by driver 28 to drive transducers 26 accordingly.

It will be appreciated that the embodiments described above are cited by way of example, and that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not disclosed in the prior art.

APPENDIX

MATHEMATICAL FORMALISM OF ULTRASOUND HOLOGRAPHIC

ALGORITHM

As explained above, an ultrasound holographic algorithm used in step 44 (Fig. 4) computes an acoustic solution to generate an arbitrary acoustic intensity in space. The calculation input is the desired intensity in space and the algorithm output is the phases and amplitudes of the phased array of acoustic transducers. Applying the phases and amplitudes to the transducer results in an acoustic field with minimal deviation in intensity relative to the desired field. We define a raster volume of the desired acoustic field intensity by TAR _X y _Z , wherein x,y,z are spatial indices and n is the iteration number of the algorithm. TAR _X y _Z is the desired intensity. TX _X y represents the complex two-dimensional pressure field at the plane of the transducers, corresponding to the phases and amplitudes of the phased array, as defined above in equation (3). The acoustic pressure in space, F _X y _Z , that is produced by the transducer array can be calculated from TX _X y using the angular spectrum method by forward propagation, as expressed by equation (2). By the same token, the pressure field TX _X y at the transducer plane can be calculated using this angular spectrum method by backward propagation from each one of the planes in TAR _X y _Z .

The holographic algorithm calculates the phases and amplitudes of the transducer elements and improves the outcome result each iteration. The iteration, of the algorithm is defined as follows:

1) Modify target field to reduce errors:

In this expression, F n-l represents the field amplitude at location x,y, which is xy normalized by the average amplitude F n-l

xyz

2) Apply target to pressure field:

F xyz TAR n

xyz ^■ F n-l

1 xyz 3) Calculate transducer plane pressure by back-propagation of F _X y _Z to TX _X y . (Each plane of F _X y _Z is back-propagated to TX _X y , and the result is the weighted average).

4) Calculate resultant pressure field by forward propagation of TX _X y to F _X y _Z .